摘要
Accurate tumor targeting,deep penetration and superb retention are still the main pursuit of developing excellent nanomedicine.To achieve these requirements,a stepwise stimuli-responsive strategy was developed through co-administration tumor penetration peptide iRGD with shape-transformable and GSH-responsive SN38-dimer(d-SN38)-loaded nanoparticles(d-SN38@NPs/iRGD).Upon intravenous injection,d-SN38@NPs with high drug loading efficiency(33.92±1.33%)could effectively accumulate and penetrate into the deep region of tumor sites with the assistance of iRGD.The gathered nanoparticles simultaneously transformed into nanofibers upon 650 nm laser irradiation at tumor sites so as to promote their retention in the tumor and burst release of reactive oxygen species for photodynamic therapy.The loaded d-SN38 with disulfide bond responded to the high level of GSH in tumor cytoplasm,which consequently resulted in SN38 release and excellent chemo-photodynamic effect on tumor.In vitro,coadministering iRGD with d-SN38@NPs+laser showed higher cellular uptake,apoptosis ratio and multicellular spheroid penetration.In vivo,d-SN38@NPs/iRGD+laser displayed advanced penetration and accumulation in tumor,leading to 60.89%of tumor suppression in 4 T1 tumor-bearing mouse model with a favorable toxicity profile.Our new strategy combining iRGD with structural transformable nanoparticles greatly improves tumor targeting,penetrating and retention,and empowers anticancer efficacy.
基金
the financial support from National Natural Science Foundation of China(Nos.81961138009
82071915)
Research Funds of Sichuan Science and Technology Department(No.19YYJC2250,China)
111 Project(No.B18035,China)
Fundamental Research Funds for the Central Universities
Natural Science Foundation of Heilongjiang Province of China(No.YQ2019H004)
作者简介
Congcong Lin,These authors made equal contributions to this work;Fan Tong,These authors made equal contributions to this work;Corresponding authors:Huile Gao,Tel./fax:+862885502532.E-mail addresses:gaohuile@scu.edu.cn;Corresponding authors:Xiangrong Yu,E-mail addresses:yxr00125040@126.com
